Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine

Cancer. 1996 Aug 15;78(4):852-7. doi: 10.1002/(SICI)1097-0142(19960815)78:4<852::AID-CNCR23>3.0.CO;2-T.


Background: When a change of opioid is considered, equianalgesic dose tables are used. These tables generally propose a dose ratio of 5:1 between morphine and hydromorphone. In the case of a change from subcutaneous hydromorphone to methadone, dose ratios ranging from 1:6 to 1:10 are proposed. The purpose of this study was to review the analgesic dose ratios for methadone compared with hydromorphone.

Methods: In a retrospective study, 48 cases of medication changes from morphine to hydromorphone, and 65 changes between hydromorphone and methadone were identified. the reason for the change, the analgesic dose, and pain intensity were obtained.

Results: The dose ratios between morphine and hydromorphone and vice versa were found to be 5.33 and 0.28, respectively (similar to expected results). However, the hydromorphone/methadone ratio was found to be 1.14:1 (5 to 10 times higher than expected). Although the dose ratios of hydromorphone/morphine and vice versa did not change according to a previous opioid dose, the hydromorphone/methadone ratio correlated with total opioid dose (correlation coefficient = 0.41 P < 0.001) and was 1.6 (range, 0.3-14.4) in patients receiving more than 330 mg of hydromorphone per day prior to the change, versus 0.95 (range, 0.2-12.3) in patients receiving ae330 mg of hydromorphone per day (P = 0.023).

Conclusions: These results suggest that only partial tolerance develops between methadone and hydromorphone. Methadone is much more potent than previously described and any change should start at a lower equivalent dose.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Hydromorphone / adverse effects
  • Hydromorphone / therapeutic use
  • Injections, Subcutaneous
  • Male
  • Methadone / adverse effects
  • Methadone / therapeutic use
  • Middle Aged
  • Morphine / adverse effects
  • Morphine / therapeutic use
  • Neoplasms / complications*
  • Pain / drug therapy*
  • Pain / etiology
  • Retrospective Studies


  • Analgesics, Opioid
  • Morphine
  • Hydromorphone
  • Methadone